Anti-vegf antibody and use thereof

Abstract

Provided is an isolated antigen binding protein capable of binding to VEGF protein and/or capable of blocking binding of VEGF protein to VEGFR protein. Further provided is a use of the isolated antigen binding protein in the preparation of a drug.

1 - 54 . (canceled) 
     
     
         55 . An antibody or antigen binding fragment capable of binding a VEGF protein, which comprises HCDR1, HCDR2 and HCDR3, wherein the HCDR1 comprises the amino acid sequence of SEQ ID NO: 9, the HCDR2 comprises an amino acid sequence selected from the group consisting of SEQ ID NOs: 14, 13 or 12, and the HCDR3 comprises an amino acid selected from the group consisting of SEQ ID NOs: 17-19. 
     
     
         56 . The antibody or antigen binding fragment according to  claim 55 , wherein the HCDR1, HCDR2 and HCDR3, respectively, comprise or consist of the following amino acid sequences:
 (1) HCDR1: SEQ ID NO: 9, HCDR2: SEQ ID NO: 14 and HCDR3: SEQ ID NO: 17;   (2) HCDR1: SEQ ID NO: 9, HCDR2: SEQ ID NO: 12 and HCDR3: SEQ ID NO: 17;   (3) HCDR1: SEQ ID NO: 9, HCDR2: SEQ ID NO: 13 and HCDR3: SEQ ID NO: 17;   (4) HCDR1: SEQ ID NO: 9, HCDR2: SEQ ID NO: 13 and HCDR3: SEQ ID NO: 18; or   (5) HCDR1: SEQ ID NO: 9, HCDR2: SEQ ID NO: 13 and HCDR3: SEQ ID NO: 19.   
     
     
         57 . The antibody or antigen binding fragment according to  claim 56 , wherein the antigen binding fragment is VHH. 
     
     
         58 . The antibody or antigen binding fragment according to  claim 56 , wherein the antibody is selected from the group consisting of: a monoclonal antibody, a chimeric antibody, a humanized antibody and a fully human antibody. 
     
     
         59 . The antibody or antigen binding fragment according to  claim 56 , which comprises H-FR1, H-FR2, H-FR3 and H-FR4, and the H-FR1, H-FR2, H-FR3 and H-FR4 are selected from any one of the following groups of amino acid sequences:
 (1) F-FR1: SEQ ID NO: 7, H-FR2: SEQ ID NO: 10, H-FR3: SEQ ID NO: 15 and H-FR4: SEQ ID NO: 20;   (2) H-FR1: SEQ ID NO: 8, H-FR2: SEQ ID NO: 11, H-FR3: SEQ ID NO: 16 and H-FR4: SEQ ID NO: 21; and   (3) H-FR1: SEQ ID NO: 8, H-FR2: SEQ ID NO: 11, H-FR3: SEQ ID NO: 16 and H-FR4: SEQ ID NO: 22.   
     
     
         60 . The antibody or antigen binding fragment according to  claim 59 , wherein the antigen-binding protein comprises a VH which comprises or consists of an amino acid sequence set forth in any one of SEQ ID NOs: 1-6. 
     
     
         61 . One or more isolated nucleic acid molecules encoding the antibody or antigen binding fragment according to  claim 56 . 
     
     
         62 . A vector comprising the nucleic acid molecule of  claim 61 . 
     
     
         63 . A cell comprising the nucleic acid molecule of  claim 61  or a vector comprising said nucleic acid. 
     
     
         64 . A method for preparing the antibody or antigen binding fragment according to  claim 56 , the method comprising culturing the a comprising one or more nucleic acid molecule encoding the antibody or antigen binding fragment or a vector comprising the nucleic acid under such a condition that the antibody or antigen binding fragment is expressed. 
     
     
         65 . A pharmaceutical composition comprising the antibody or antigen binding fragment according to  claim 56 , the nucleic acid molecule encoding said antibody or antigen binding fragment, the vector of comprising said nucleic acid and/or the cell comprising said nucleic acid or said vector, and optionally a pharmaceutically acceptable carrier. 
     
     
         66 . A polypeptide comprising the antibody or antigen binding fragment according to  claim 56 . 
     
     
         67 . An immunoconjugate comprising the antibody or antigen binding fragment according to  claim 56  or a polypeptide comprising said antibody or antigen binding fragment. 
     
     
         68 . A method for preventing, alleviating or treating tumor, the method comprising administering the antibody or antigen binding fragment according to  claim 56 , one or more nucleic acid molecule encoding said antibody or antigen binding fragment, a vector comprising said nucleic acid, a cell comprising said nucleic acid or said vector or a pharmaceutical composition comprising said antibody or antigen binding fragment or the polypeptide comprising said antibody or antigen binding fragment and/or an immunoconjugate comprising said antibody or antigen binding fragment or the polypeptide to a subject in need thereof. 
     
     
         69 . The method according to  claim 68 , wherein the tumor is a VEGF-overexpressing tumor. 
     
     
         70 . The method according to  claim 68 , wherein the tumor is a solid tumor and/or a non-solid tumor. 
     
     
         71 . The method according to  claim 68 , wherein the tumor is lung cancer, colorectal cancer, breast cancer, kidney cancer, gastric cancer, liver cancer, blastoma, cervical cancer and/or ovarian cancer. 
     
     
         72 . A method for inhibiting the binding of VEGF protein to VEGFR protein, comprising administering the antibody or antigen binding fragment according to  claim 56 , one or more nucleic acid molecule encoding said antibody or antigen binding fragment, a vector of comprising said nucleic acid, a cell comprising said nucleic acid or said vector or a pharmaceutical composition comprising said antibody or antigen binding fragment or a polypeptide comprising said antibody or antigen binding fragment and/or an immunoconjugate comprising said antibody or antigen binding fragment or the polypeptide to a subject in need thereof.